This is a renewal of additional studies of fundamental aspects of the neurobiology of Alzheimer's Disease. In Project I, will continue studies of the biochemistry and molecular biology of A68, the antigen recognized by the monoclonal antibody Alz-50. The antigen has been purified to homogeneity and sequencing studies are in progress. The purified antigen appears to contain a protein kinase activity. In Project II, will continue to investigate the nature of cDNA probes obtained using antibodies recognizing neurofibrillary tangles. A cDNA encoding a portion of the MAP2 sequence has been identified to contain the binding site for the regulatory subunit of the cyclic AMP dependent protein kinase. Possible abnormalities in the concentration of the regulatory subunit will be investigated. Interactions of proteins encoded by these and other cDNA's with other cellular proteins will be investigated. In Project III, Drs. Dickson, Mattiace and Yen will continue and extend their studies of senile plaque formation, extending studies of human brain by examination of microglial cells in tissue culture and studies of neuritic abnormalities in rat brain. A new project has been added, Dr. Hanna Ksiezak-Reding will investigate the involvement of posttranslational modifications of tau protein in tangle formation and neuritic abnormalities in Alzheimer's Disease. The possible role of alternate splice variants of tau will also be investigated in Alzheimer's Disease, and in brain development.